Present modalities of treatment for malignant tumors and particularly malignant brain tumors include amongst others surgery, radiation therapy, and chemotherapy. However, the treatment of malignant brain tumors has a very poor prognosis for survival. Furthermore, the quality of life of survivors during and after treatment is typically poor. Clinical evidence indicates that hyperthermia treatment with modest increases in the temperature of cancerous tissue cells has led to the regression, disappearance, and on some occasions cure of malignant tumors. Hyperthermia is more cytotoxic to neoplastic cells than normal cells, because neoplastic cells are oxygen deprived, nutritionally deficient, and low in pH making them incapable of tolerating the stress imposed by elevated temperature.
The major forms of energy for generating hyperthermia presently include microwaves, radio frequency induction, radio frequency localized current, and ultrasound. Most of the techniques used to dispense these are non-invasive, i.e., the heat generating source is external to the body and does not invade the body. Several problems exist with these non-invasive techniques. First, the energy must pass through the skin surface, and, as a result, a substantial amount of power is absorbed by normal body tissue. One consequence is severe skin burns. Second, these external heating sources cause nonuniform temperature profiles throughout the tumor and increased temperatures in normal tissue. Nonuniform heating does not assure destruction of the tumor at cold spots. Whereas, unwanted destruction of normal tissue may occur at hot spots.
Studies indicate that tumor mass reduction by hyperthermia is related to the thermal dose. Thermal dose is the minimum effective temperature applied throughout the tumor mass for a defined period of time. Hot spots and cold spots which occur with microwave hyperthermia may cause increased cell death at the hot spots, but ineffective treatment at cold spots results in future tumor growth.
Others have attempted the use of interstitial techniques to obtain local hyperthermia, with limited success. Interstitial heating of brain tumors through an implantable microwave antenna has been investigated. However, microwave probes are ineffective in producing precisely controlled heating of tumors. Temperature may deviate as much as 10 degrees Celsius from the desired target temperature. Besides, microwave activity adversely affects cellular structures and their integration, regardless of other thermal effects. The result is, again, nonuniform temperatures throughout the tumor. Such variations are a result of the microwave antenna's inability to evenly deposit energy throughout the tissue.
Efferent blood flow is a major cause of heat loss for tumors being heated, and blood flow varies throughout the tumor. As a result, uneven heating results even if energy is delivered uniformly throughout the volume of the tumor. To be effective, the application and deposition of thermal energy to the tumor must be precisely controlled to compensate for the variations in blood flow. In addition, the therapy itself will perturb the tumor's vascular system during treatment causing variations in local perfusion around the probe. Thus, heat loss from a tumor will be time dependent and affected by the hyperthermia treatment. This demonstrates the need to both monitor and control the temperature in multiple regions of the tumor throughout treatment.
Another brain tumor treatment, chemotherapy, also has a number of problems. The perfusion of agents from the blood to brain cells is much lower than that from the blood to other cells. This phenomenon, commonly known as the blood-brain barrier, prevents chemotherapeutic agents from effectively treating brain tissue having neoplastic cells. Increasing the concentration levels of these agents in blood, however, does not necessarily result in increased delivery of these agents to the tumor site. Another problem is the damage to normal tissue. This problem is, of course, weighed against the effects of unchecked tumor growth. In addition, the side effects of these high concentration level agents in the patient typically create a poor quality of life during and after treatment. Still another problem is the effective life of the agent, which may be as short as 15 to 20 minutes. Getting a short life agent intravenously to a brain tumor in a timely manner and for an extended period of time complicates the delivery process. Controllably releasing an agent in a cyclical manner further complicates the process.
Studies have shown that elevating the temperature of various chemotherapeutic drugs only a few degrees Celsius increases the effectiveness level of the drug significantly. The added benefits of treating a malignant tumor with these drugs at temperatures elevated above normal body temperatures are significant. However, a major problem is delivering these drugs while either maintaining the temperature thereof at a controlled elevated level for any extended period of time or raising the temperature of the drug to the control level once delivered to the tumor site.
Radiation therapy is another modality available for treating cancer. Radiation therapy has the disadvantage of killing healthy as well as cancerous tissue in the exposed area. For brain tumor regression, radiation therapy is perhaps the most effective treatment. However, as a result of radiation treatments at levels adequate for tumor remission, radiation necrosis, a self-destruction of normal brain tissue, renders patients mentally and physically nonfunctional with symptoms similar to Alzheimer's disease.
Studies have shown that such modalities of treatment have limited degrees of success when provided singly. These studies have also indicated that the effectiveness level of radiation therapy is elevated when provided concomitantly with other treatment modalities such as chemotherapy and hyperthermia, thereby providing synergistic effects.